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A Study of Durvalumab With or Without Tremelimumab in Endometrial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03015129
Recruitment Status : Active, not recruiting
First Posted : January 9, 2017
Last Update Posted : May 1, 2020
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
This study will test the safety and efficacy of the experimental drug called durvalumab with or without another experimental drug called tremelimumab in endometrial cancer.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Endometrial Carcinosarcoma Endometrial Carcinoma Endometrial Cancer Recurrent Endometrial Carcinoma, Recurrent Drug: Durvalumab Drug: Tremelimumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of Durvalumab [MEDI4736](Anti-PD-L1 Antibody) With or Without Tremelimumab (Anti-CTLA-4 Antibody) in Patients With Persistent or Recurrent Endometrial Carcinoma and Endometrial Carcinosarcoma
Study Start Date : January 2017
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021


Arm Intervention/treatment
Experimental: Durvalubmab
Patients will receive intravenous infusion of durvalumab 1500mg Fixed Dose every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.
Drug: Durvalumab
Experimental: Durvalubmab + Tremelimumab
Patients will receive 1500mg Flat Dose durvalubmab via intravenous infusion every 4 weeks for up to 4 cycles and 75mg tremelimumab via intravenous infusion every 4 weeks for up to 4 cycles, and then continue 1500mg Fixed Dose durvalumab every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.
Drug: Durvalumab
Drug: Tremelimumab



Primary Outcome Measures :
  1. Treatment Efficacy determined by measuring the Overall Response Rate [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have recurrent or persistent endometrial carcinoma (including: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma) or endometrial carcinosarcoma). Histologic documentation of diagnosis of carcinoma is required.
  • All patients must have measurable disease. Measurable disease is defined by RECIST (version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI.
  • Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1 (Section 8.1). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
  • Age ≥ 18 years and life expectancy of ≥ 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Resolution of (non-laboratory) adverse effects of recent surgery, radiotherapy, or chemotherapy to Grade ≤1 prior to first study treatment (with the exception of alopecia or neuropathy).
  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of endometrial carcinoma or carcinosarcoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen.
  • Patients are allowed to receive, but are not required to receive, three additional cytotoxic regimen for management of recurrent or persistent disease. Hormonal therapies will not count toward the prior regimen limit.
  • Adequate normal organ and marrow function defined by the following laboratory results obtained within 14 days prior to first treatment:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
    • Platelet ≥ 100 x 10^9/L (>100,000 per mm^3)
    • Hemoglobin ≥ 9.0 g/dL
    • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (Unless Gilbert's Syndrome, without concurrent clinically significant liver disease)
    • AST (SGOT)/ALT (SGPT) ≤ 3 x institutional upper limit of normal unless (ULN) liver metastases are present, in which case it must be ≤ 5x ULN
    • Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)
  • Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥55 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Patients must have been enrolled, or agree to consent to the companion genomic profiling study MSKCC IRB# 12-245. Results must be available before starting treatment on protocol.
  • Patients must have signed an approved informed consent and authorization permitting release of personal information.

Exclusion Criteria:

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site); Previous enrollment in the present study.
  • Participation in another clinical study with receipt of an investigational product during the last 4 weeks
  • Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or any anti-CTLA4, including tremelimumab.
  • History of another primary malignancy except for:

    • Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    • Adequately treated carcinoma in situ without evidence of disease (eg, cervical cancer in situ)
    • Adequately treated stage 1 breast cancer.
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) < 21 days prior to the first dose of study drug. Receipt of the last dose of hormonal therapy within < 7 days prior to the first dose of study drug.
  • Any prior radiation therapy must be discontinued at least four weeks prior to registration.
  • At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy) There is no delay in treatment for minor procedures (e.g., central venous access catheter placement).
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs)
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or durvalumab and tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone for nausea or steroids as CT scan contrast premedication) may be enrolled.
  • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > Grade 1
  • Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • History of primary immunodeficiency
  • History and/or confirmed pneumonitis or interstitial lung disease
  • History of allogeneic organ transplant
  • History of hypersensitivity to durvalumab or any excipient
  • History of hypersensitivity to tremelimumab
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  • Known history of previous clinical diagnosis of tuberculosis
  • History of leptomeningeal carcinomatosis
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
  • Subjects with uncontrolled seizures.
  • Patients who are pregnant or breastfeeding or patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period
  • History of small or large bowel obstruction within 3 months of registration, including subjects with palliative gastric drainage catheters. Subjects with palliative diverting ileostomy or colostomy are allowed if they have been symptom-free for more than 3 months.
  • Ongoing bowel perforation or presence of bowel fistula or abscess within 3 months of registration.
  • Subjects with refractory ascites, defined as ascites needing drainage catheter or therapeutic paracentesis more often than every 4 weeks.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03015129


Locations
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United States, New Jersey
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States, 07920
Memoral Sloan Kettering Monmouth
Middletown, New Jersey, United States, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States, 07645
United States, New York
Memorial Sloan Kettering Commack
Commack, New York, United States, 11725
Memoral Sloan Kettering Westchester
Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan Kettering Nassau
Uniondale, New York, United States, 11553
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Vicky Makker, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03015129    
Other Study ID Numbers: 16-1491
First Posted: January 9, 2017    Key Record Dates
Last Update Posted: May 1, 2020
Last Verified: April 2020
Keywords provided by Memorial Sloan Kettering Cancer Center:
Durvalumab
MEDI4736
Tremelimumab
anti-PD-L1 Antibody
anti-CTLA-4 antibody
16-1491
Additional relevant MeSH terms:
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Carcinosarcoma
Mixed Tumor, Mullerian
Carcinoma
Endometrial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Neoplasms, Complex and Mixed
Sarcoma
Neoplasms, Connective and Soft Tissue
Durvalumab
Tremelimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents